Outcome for triple negative breast cancer in a retrospective cohort with an emphasis on response to platinum-based neoadjuvant therapy

Abstract

Purpose: The rate of pathological complete response (pCR) for patients with triple negative breast cancer (TNBC) is increased when carboplatin is added to neo-adjuvant chemotherapy (NACT). However, while phase III trial data showing a survival benefit are awaited, carboplatin is not yet standard-of-care for TNBC. The aim of this study was to examine the rate of pCR and the outcome for those treated with carboplatin and to examine the predictors of response to therapy.

Methods: The retrospective series comprised 333 consecutive patients with TNBC (median follow-up time, 43 months). Adjuvant chemotherapy was given to 51% (n = 168) of patients and 29% (n = 97) received anthracycline-taxane NACT with carboplatin given to 9% (n = 31) of patients.

Results: Overall, 25% (n = 78) of patients experienced a breast cancer recurrence and 22% (n = 68) died from disease. A pCR breast and pCR breast/axilla was more common in those who received carboplatin (n = 18, 58% and n = 17, 55%, respectively) compared those who did not (n = 23, 36% and n = 18, 28%, respectively) (p = 0.041 and p = 0.011, respectively). By multivariable analysis, carboplatin and high tumor grade were independent predictors of pCR breast/axilla (OR_non-pCR = 0.17; 95% CI 0.06-0.54; p = 0.002; and OR_non-pCR = 0.05, 95% CI 0.01-0.27; p < 0.001, respectively). pCR breast/axilla was an independent predictor of DFS (HR_non-pCR=6.23; 95% CI 1.36-28.50; p = 0.018), metastasis-free survival (HR_non-pCR = 5.08; 95% CI 1.09-23.65; p = 0.038) and BCSS (HR_non-pCR = 8.52; 95% CI 1.09-66.64; p = 0.041).

Conclusion: Carboplatin therapy and high tumor grade are associated with a significant increase in the rate of pCR, which is an independent predictor of outcome. These data support the use of carboplatin in NACT for TNBC, while results from phase III studies are awaited.

Keywords: Breast cancer; Carboplatin; Neoadjuvant; Pathological complete response; Survival; Triple negative.

Fig. 1

Disease-free, metastases-free and breast cancer-specific survival for patients according to schedule of chemotherapy. Kaplan–Meier cumulative survival curves for a disease-free survival and b metastases-free survival for patients who received adjuvant chemotherapy (CT) (n = 168), neoadjuvant CT (n = 93) or no CT (n = 55) (log-rank test DFS, p value = 0.024) and (log-rank test MFS, p value = 0.045). c Kaplan–Meier cumulative survival curves for breast cancer-specific survival for patients for patients who received adjuvant therapy (n = 161), neoadjuvant CT (n = 96) or no CT (n = 64) (log-rank test, p value < 0.001)

Fig. 2

Disease-free, metastases-free and breast cancer-specific survival according to pathological response to NACT. Kaplan–Meier cumulative survival curves show the association between pathological complete response (pCR) breast/axilla and a disease-free survival (n = 93) log-rank test, p value = 0.003; b metastases-free (n = 93) log-rank test, p value = 0.007; and c breast cancer-specific survival (n = 96) log-rank test, p value = 0.005. A pCR breast/axilla is defined as ypT0/isN0

Fig. 3

Disease-free survival for patients who received NACT according to the administration of platinum agents. Kaplan–Meier curves show the disease-free survival for patients stratified according to the administration of platinum-based NACT. The analysis was confined to 24-month follow-up period because the follow-up time for patients who received a platinum agent was short. A new event was observed in two of 31 patients who received a platinum and in 12 of 60 patients who received standard anthracycline–taxane-based NACT (log-rank test, p value = 0.262)